The emergence of new biotherapeutics is both the driver and result of innovative drug development technologies.

Next-Gen Therapies Drive Development Technologies

Moderna initiates BLA submission; GSK Earns EUA for mAb Treatment

Vaccine Makers Plan for Global Distribution

Mass spectrometry and automation are growing in importance for protein characterization.

Unraveling Protein Characteristics

The COVID-19 pandemic has triggered additional considerations to supplier oversight.

Are Your Contract Manufacturing Facilities Up to Speed?

The Janssen Pharmaceutical Companies of Johnson & Johnson announced on June 1, 2021 that FDA has granted breakthrough therapy designation for teclistamab, an off-the-shelf, T-cell redirecting, bispecific antibody, for treating relapsed or refractory multiple myeloma. FDA’s designation follows a priority medicines (PRIME) designation granted by the European Medicines Agency in January this year. In 2020, the European Commission and FDA each granted teclistamab orphan drug designation for the treatment of multiple myeloma.

Teclistamab targets both B-cell maturation antigen (BCMA), which is expressed at high levels on multiple myeloma cells, and CD3 receptors. The bispecific antibody redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumor cells. Results from preclinical studies demonstrated that teclistamab kills myeloma cell lines and bone marrow-derived myeloma cells from heavily pretreated patients. Teclistamab is currently in Phase II clinical development and is also being explored in combination studies.

“We are pleased to have received [b]reakthrough [t]herapy and PRIME [d]esignations for our novel bispecific antibody, teclistamab,” said Peter Lebowitz, MD, PhD, Global Therapeutic Area head, Oncology, Janssen Research & Development, in a company press release. “This program exemplifies our commitment to advancing science for patients living with multiple myeloma, and it builds upon our robust portfolio in this disease.”

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FDA has granted Janssen breakthrough therapy designation for teclistamab, an investigational bispecific antibody under development for treating relapsed or refractory multiple myeloma.

Janssen Receives FDA Breakthrough Therapy Designation for Multiple Myeloma mAb

On June 07, 2021, FDA announced the approval of Biogen’s Aduhelm (aducanumab), a new monoclonal antibody for treating Alzheimer’s disease, using the accelerated approval pathway. Aduhelm represents a first-of-its-kind treatment approved for Alzheimer’s disease and is the first new treatment approved for the disease since 2003, the agency stated in its press release.

FDA also noted in its press release that this drug is the first therapy that targets the fundamental pathophysiology of the disease. Researchers evaluated Aduhelm’s efficacy in three separate double-blind, randomized, placebo-controlled dose-ranging studies that represent 3482 patients in total. The results from the studies showed that patients receiving the treatment had significant dose-and time-dependent reduction of amyloid beta plaque, while patients in the control arm of the studies had no reduction of amyloid beta plaque, the plaques being the hallmark of Alzheimer’s disease. These results support the accelerated approval of the drug.

Under the accelerated approval provisions, FDA is requiring Biogen to conduct a new randomized, controlled clinical trial to verify the drug’s clinical benefit. If the trial fails to verify clinical benefit, FDA may initiate proceedings to withdraw approval of the drug.

Aduhelm was also granted fast track designation, which serves to expedite the development and review of drugs that are intended to treat serious conditions when initial evidence shows that the drug has potential to address an unmet medical need.

“Alzheimer’s disease is a devastating illness that can have a profound impact on the lives of people diagnosed with the disease as well as their loved ones,” said Patrizia Cavazzoni, MD, director of FDA’s Center for Drug Evaluation and Research, in the press release. “Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s. As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”

FDA has granted accelerated approval to Biogen for Aduhelm (aducanumab), a new mAb treatment for Alzheimer’ disease.

FDA Grants Accelerated Approval for Biogen’s Alzheimer’s Drug

 Washington Editor, jillwechsler7@gmail.com.

In laying out its formal budget proposal for fiscal year 2022, the Biden administration supports a notable increase in funding for public health and research as a lead priority for the coming year. While Congress will reject or modify many of the specifics, the federal government’s remarkable success in combatting the COVID-19 pandemic continues to generate bipartisan support for advancing biomedical research and public health and safety.

FDA’s oversight and guidance in speeding the development of critical COVID-19 vaccines, diagnostics, and therapies is rewarded with additional funding to continue and strengthen those capabilities. The 

requests $6.5 billion for the agency, up 8%, with $3.6 billion in public appropriations and $2.9 billion in user fees paid by industry. The added $344 million, according to the 

, is allocated primarily to three main areas: critical public health infrastructure, including data modernization and expanded laboratories, facilities, and staff; core safety programs for food and medical products and global supply chains; and ensuring public health by increasing secure inspections, promoting health equity, and addressing the opioid crisis.

Among the specifics, FDA seeks $19 million to enable its field inspection program to carry out site visits delayed by the pandemic and to avoid a reduced frequency in both domestic and foreign inspections going forward. To help end the opioid crisis, FDA would gain $38 million to support research for developing overdose reversal treatments and new non-opioid pain medications and to devise systems to better track and manage opioid use.

For several years now, FDA has emphasized the need to modernize its data and communications systems for medical products and food, and the new budget may finally advance its Enterprise Technology and Data modernization efforts. An additional $45 million would support wider use of artificial intelligence and advanced IT systems to enable data sharing across product centers and ease communications among agency offices, streamline core business processes, and better track medical product manufacturing to better anticipate shortages.

The budget plan also cites the need for legislation to make permanent certain temporary policies that will expire with the end of the current public health emergency. This includes authority to require medical device manufacturers to notify FDA of product shortages, to request records and other information from medical device makers and clinical research sites in advance or “in lieu of” a physical facility inspection, and to require data and studies from drug manufacturers to extend product expiration dates as a way to prevent product shortages.

The Biden spending plan further outlines initiatives to enhance public health more broadly, including programs to address gun violence and the opioid epidemic and to continue investment in biomedical research to prepare for future pandemics. Reforms that allow Medicare to negotiate prices with drug manufacturers and impose rebates on companies that raise prices faster than inflation would save more than $500 billion over 10 years, the analysts calculate, but without offering many specifics for implementing such contentious changes.

While the National Institutes of Health (NIH) would see a hefty 22% rise in funding for a $50.5 billion 2022 budget, $6.5 billion of that increase would fund the new Advanced Research Projects Agency for Health (ARPA-H) within NIH, a hot-button proposal that has raised many questions. Designed as a parallel to the Defense Department’s Defense Advanced Research Projects Agency (DARPA), stakeholders already are debating if ARPA-H should reside within NIH or be independent, how it could advance “transformational” research issues for multiple diseases, and how its projects would involve private sector R&D and technology transfer. A 

review of the ARPA-H initiative from the Congressional Research Service 

summarizes these issues and options for going forward.

The administration also seeks an $8.5 billion budget for the Centers for Disease Control and Prevention (CDC), a notable $1.5 billion increase (up 21%) in funding for this usually neglected agency. And the Biomedical Advanced Research and Development Authority would gain $227 million for a $823 million spending plan to build the national stockpile and help prepare for future pandemics.

Congressional debate on FDA’s budget will begin June 10 at a hearing before the Senate Appropriations subcommittee that deals with the agency. Acting Commissioner Janet Woodcock will make the case for the administration’s spending plan and FDA program priorities, and again before the relevant House appropriations subcommittee. But the main decisions on budget support for the agency will turn on broader revenue and spending issues for federal programs as the nation continues to promote economic growth and public health recovery.

The Biden administration supports a notable increase in funding for public health and research as a lead priority for the coming year. 

Biden Budget “Wish List” Maps FDA and Health Care Priorities

Emerson announced in a June 3, 2021 press release that it has integrated the emerging Module Type Package (MTP) process automation standard into its control systems for both distributed control systems (DCS) and programmable logic controllers (PLCs). The MTP standard from the User Association of Automation Technology in Process Industries (NAMUR) is a common, open standard that requires less engineering. NAMUR’s standard allows companies to use MTP tools to make new equipment integration closer to “plug-and-play,” which facilitates operations changes to accommodate new products.

MTP eliminates the need for end users or system integrators to invest in additional engineering or special integration tools. By using MTP tools to integrate manufacturing skids and their respective automation systems, Emerson estimates manufacturers and system integrators could save weeks in project time and hundreds of thousands of dollars in engineering costs compared to traditional integration without MTP. MTP helps enable flexible manufacturing, such as ballroom-style facilities where skids can be interchanged with minimal re-engineering.

“MTP is a significant step to help the manufacturing industries respond faster to changing markets,” said Sean Sims, Emerson’s vice-president of marketing for the DeltaV platform, in the press release. “With our MTP implementation, Emerson is continuing a tradition of not only supporting but innovating on industry standards. Integration between our DeltaV and PACSystems automation systems as well as third-party automation systems will help create more modular, flexible manufacturing that improves speed to market for our customers.”

Along with the first MTP release, Emerson has made reliability data from its manufacturing units importable to the DeltaV system. Operators can use the asset health data from the AMS Asset Monitor edge analytics device to consider how the health of plant asset will impact operations and production. Emerson’s MTP tools natively create a configuration file for its PACSystems PLCs and AMS machinery prediction devices that is automatically integrated into the DeltaV DCS, Emerson explained in the press release.

The Module Type Package standard is now supported in Emerson’s DCS and PLCs. 

Emerson Integrates MTP Process Automation Standard into Control Systems

, James Blackwell, president of The Windshire Group, LLC, discusses stumbling blocks to process development; strategies for developing, scaling up, and scaling out bioprocesses; and challenges when working across multiple sites.

Well-defined studies are crucial to effective process development.

Common Challenges in Cross-Functional Process Development

Advanz Pharma has announced, in a June 1, 2021 press release, that its acquisition by Nordic Capital—a subsidiary of Nordic Fund X Epsilon, Cidron Aida Bidco Limited—has now completed. The deal was struck for $846 million.

“This deal is fantastic news for Advanz Pharma and our goal of becoming the go-to partner for complex medicines in Europe. Nordic Capital will be pivotal in helping the business through both its deep sector expertise and access to capital that will enable considerable investment in our organic and inorganic pipeline. This partnership will be essential in allowing us to further broaden choice for both prescribers and patients throughout the world and ensure access to the essential medicines we supply,” said Graeme Duncan, CEO of Advanz Pharma, in the press release. “This deal could not have been possible without our employees whose hard work has been instrumental in collectively contributing towards building Advanz Pharma into the strong and diverse company it is today.”

Raj Shah, partner and head of Healthcare, Nordic Capital Advisors, added, in the press release, “Advanz Pharma’s vision and regional focus fully aligns with Nordic Capital’s expertise and deep knowledge of European market sectors. We are delighted to be able to support Advanz Pharma at this exciting juncture in their journey. Nordic Capital will help fuel the company’s strategic growth and allow it to invest in future pipeline and M&A activities so that even more patients can access critical medicines now and in the future.”

The acquisition of Advanz Pharma by Nordic Capital has now completed, in a deal worth $846 million.

Nordic Capital Acquires Advanz Pharma for $846 Million

Hovione announced on May 27, 2021 that it has entered into a strategic collaboration with the Institute of Experimental and Technological Biology (iBET), a research and development (R&D) institution.

Hovione was previously a founding member of the institution in 1989 and re-joined to increase its R&D programs in the areas of novel and high potential pharmaceutical technologies, while combining expertise for industrial innovation in new therapeutic fields, Hovione said in a company press release.

“We are delighted with the return of Hovione to the membership of iBET,” said Paula Alves, CEO, iBET, in the press release. “Our goal is to strengthen the R&D capabilities of our members; this important partnership with Hovione will allow [our members] to pool together complementary scientific competencies and power the development of biopharmaceuticals that are essential to patient health. To win in the area of biologics and novel therapies it is critical to have access to state-of-the art competencies and support technologies.”

“The partnership with IBET opens a new chapter in Hovione's history,” added Guy Villax, CEO of Hovione, in the press release. “We will bring together our knowledge in chemistry [and] in cutting-edge technologies [as well as our knowledge] of the market and of the FDA regulatory process with iBET’s command of cell biology, viral biology, and bioprocessing. If the twentieth century was the century of chemistry, the 21st century is the one of biology. iBET scientists have built deep knowledge in specific areas; we plan to work together to turn that knowledge into industrial innovation.”

Hovione has re-joined iBET to increase its R&D programs in novel and high potential pharmaceutical technologies and to combine expertise for industrial innovation in new therapeutic fields.

Hovione to Re-Join iBet

Aceto, a provider of specialty materials for life sciences and advanced technology markets, announced on June 2, 2021 that it has acquired Cascade Chemistry, a US-based manufacturer of active pharmaceutical ingredients (APIs), regulatory starting materials, and advanced intermediates.

Through the acquisition, Aceto can now offer its customers support throughout the drug development process and access to North American manufacturing for APIs and advanced intermediates, Aceto said in a company press release.

“The acquisition of Cascade Chemistry supports and complements our focus on acquisitions that offer customers supply chain choice and technical expertise. With each of our acquisitions, Aceto looks to add companies that enhance our business capabilities and support our growth strategy, while aligning with our core business values,” said Gilles Cottier, CEO of Aceto, in the press release. “We aim to ensure that all our customers have access to robust solutions that are tailored to their needs and allow them to advance their compounds into clinical trials with confidence and efficiency. Cascade Chemistry is an excellent addition to the Aceto team.”

“Cascade Chemistry has a 40-year track record of applying our deep expertise to solve problems and provide our customers with the support they need to successfully complete the challenging and complex API development cycle,” added Jeremiah Marsden, president of Cascade Chemistry, in the press release. “We are proud of our reputation for quality and outstanding customer service and we welcome the opportunity to now join forces with Aceto. Access to the expanded capabilities of the Aceto family of companies will allow us to serve our clients with comprehensive, fully integrated support teams and additional service options that will further enhance and accelerate our clients’ programs.”

Through the acquisition, Aceto can now offer its customers support throughout the drug development process and access to North American manufacturing for APIs and advanced intermediates.

Aceto to Acquire Cascade Chemistry

Recro Pharma, a contract development and manufacturing organization (CDMO), announced on June 2, 2021 that it has expanded the clinical capabilities of its clinical trial services (CTS) offerings.

The added capabilities include clinical-scale sachet and blister packaging for clinical trial pharmaceuticals and a relationship with a European Union Qualified Person (QP) for its CTS offerings, the company said in a press release. Based on an audit completed by the QP, Recro meets the relevant GMP manufacturing standards and requirements for clinical trial materials to be used in the European Union.

“While our addition of CTS offerings is not yet a year old, it has already provided opportunities for our existing clients to expand their scope of work with Recro, as well as serving as a gateway for attracting new customers. This is highlighted by the fact that our recent expansion of packaging services has played an important role in increased client interest and attracting new business,” said Scott Rizzo, senior vice-president and general manager of Recro, in the press release. “In addition to the growing traction of the CTS offerings in the US, we are now positioned to carry momentum into the European market based on the successful QP audit. Taken together, these expanded capabilities will allow us to continue the positive trajectory for our CTS offerings, which typically have the benefit of a shorter sales and earnings cycle, as they become a more meaningful contributor to the overall growth of Recro.”

The added capabilities include clinical-scale sachet and blister packaging for clinical trial pharmaceuticals and a relationship with a European Union Qualified Person for its CTS offerings.

Recro to Expand its Clinical Trial Services Offerings

Industry consortiums have always been an important aspect of the bio/pharmaceutical space as they bring together key industry members to combine their individual resources to meet a common goal. Now more than ever, with COVID-19 still taking the world by storm, industry consortiums are necessary to advance specific programs and treatments aimed at stopping the spread of the disease.

For example, the National Institutes of Health (NIH) formed the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership in April 2020 to coordinate research strategies and fast-track the development of COVID-19 vaccines and treatments. The group consists of the Foundation for the National Institutes of Health; NIH’s sibling agencies in the Department of Health and Human Services, including the Biomedical Advanced Research and Development Authority, Centers for Disease Control and Prevention, and FDA; government agencies including the Department of Defense and the Department of Veterans Affairs; Countermeasures Acceleration Group (formerly known as Operation Warp Speed); the European Medicines Agency (EMA); and representatives from academia, philanthropic organizations, and biopharmaceutical companies.

With the support of other industry leaders, NIH has made strides in COVID-19 research by expanding its knowledge of viral biology and pathogenesis of SARS-CoV-2, the virus that causes COVID-19, in order to properly develop the tools needed to diagnose, treat, and prevent the disease.

Similarly, the COVID R&D Alliance, a consortium of therapeutic drug R&D leaders formed in March 2020, seeks to accelerate COVID-19 therapies and treatments by combining their resources and studies. Elliott Levy, MD, former senior vice-president of R&D at Amgen and a member of the COVID R&D Alliance, details how the group came about and the challenges and successes they have faced since banding together.

What steps were taken to form this Consortium?

 The COVID R&D Alliance came together organically when R&D leaders from across the industry began talking to each other about the emerging global pandemic and how to effectively study potential therapeutics and vaccines for COVID-19 when information about the virus was incomplete and evolving in real time.

Specifically, on a Saturday morning conference call in March 2020, R&D leaders from GlaxoSmithKline (GSK), Amgen, Takeda, and several other large biopharma companies committed to forming an alliance to streamline R&D efforts to expedite the development of therapies for COVID-19. This began with establishing areas of focus, screening late-stage molecules, and testing approved drugs for efficacy against the virus. It expanded into sharing pre-competitive information and engaging in adaptive platform trials to efficiently test candidates.

Was it challenging to find companies willing to participate in this Consortium?

 Not at all. In fact, we continue to receive inquiries from companies across the life sciences and biotech industries asking how they can help. There was an overall sense that the industry needed to step up and work together to help solve this challenge because we are experts at studying, developing, and manufacturing therapies and vaccines.

Why are Industry Consortiums important when it comes to COVID-19 research and advancements?

 Government agencies and Non-Government Organizations (NGOs) played an important role in the response to COVID-19, however, there are gaps that exist that the industry is best suited to fill. Governments and NGOs often focus their efforts on early-stage research and late-stage manufacturing and distribution. Industry can fill the gap in between. Pharmaceutical companies conduct mid- and late-stage research and can advance promising candidates through large-scale trials. By creating a consortium, we were able to communicate and collaborate – which allowed us to avoid duplicating efforts, quickly share findings, and focus on areas that were most promising. This model can also be used going forward to prepare for future epidemics.

How challenging or difficult has it been to help advance COVID-19 research throughout the pandemic? Are there specific key areas of focus where the research is aimed?

 The pandemic created many new research challenges that the biopharma industry had never faced. The first being ability to perform trials.

Specifically, within COVID-19 related trials, there were many challenges. Initially, trials across the world were testing the same compounds – many of which were later proven to be ineffective, like hydroxychloroquine. Sites and investigators faced difficulties synchronizing recruitment with the ebbs and flows of outbreaks. And there were other challenges, such as ensuring diversity in trial populations, educating health care providers, getting sites online, and a myriad of other issues stemming from a crowded space of institution trying to help sick patients.

The Alliance sought to address many of these challenges by participating in and launching adaptive platform trials, such as REMAP COVID, I-SPY COVID, and others. One adaptive, platform trial sponsored by Amgen called COMMUNITY was set up with the intent of allowing other life science companies to enter and test candidates and/or existing medicines that might have potential efficacy against COVID-19 symptoms. COMMUNITY trial sites were located across the world.

Given the speed of the disease, testing repurposed therapies was one strategy attempted. Ultimately, almost none of the repurposed therapies tested against COVID-19 showed efficacy. New monoclonal antibodies have shown benefits, but due to their sophisticated administration and cost, they are not currently available to much of the world.

This leads to one of the most important lessons we have learned from the pandemic: we are already too late if candidate development begins when outbreaks start. Due to globalization, it is likely more epidemics will emerge. Effective small molecule therapies and antivirals are critical to mitigate such pathogens, but they cannot be identified and studied fast enough if we don’t start before an outbreak strikes. Essentially, we must begin developing antiviral assets for the next potential epidemics now.

Do you have any specific examples of how you have helped further COVID-19 research?

In terms of quantifiable results, member companies in the Alliance helped to:

Bring together 20+ global life science and biotech companies and created an open line of pre-competitive communication that will have some enduring implications as those collaborations are into new pandemic preparedness initiatives.

Screen 4500+ pre-clinical compounds expediently – preventing inefficient studies, testing, and trials.

Create an ecosystem of pre-competitive clinical trial and real-world data sharing that can be leveraged in the future study of other diseases in the future. In fact, eight members of the Alliance published an article in BioCentury laying out a shared vision for the future of expanded data sharing.

Alliance members have entered candidates into multiple adaptive platform trials (REMAP, I-SPY, COMMUNITY). COMMUNITY was an adaptive platform trial launched by the industry, and individual members have launched dozens of trials. Results of these trials are being released as they occur so scientists worldwide can learn from them.

Member companies also developed three COVID-19 vaccines that gained FDA, EUA, and two monoclonal antibodies therapies are currently in use today.

As COVID-19 continues to spread, industry leaders are banding together to stop the disease in its tracks. 

Industry Consortiums Work to Tackle COVID-19

Cytiva has acquired the German scientific software maker GoSilico, the company announced in a June 2, 2021 press release. GoSilico’s simulation software is used to build digital twins of downstream processing to speed process development using mechanistic modelling to replace physical experiments.

“The powerfully innovative digital solution created by GoSilico will bring great value to our customers, who can use mechanistic models to improve their decisions, accelerate their process development, and more quickly bring new therapies to market,” said Olivier Loeillot, vice-president, Cytiva, in the press release.

“Our entire team is excited to join the Cytiva family. With Cytiva’s global presence and broad base of customers, our mechanistic modelling technology will reach more drugmakers, ultimately enabling a more robust process development and a more efficient path to bring new therapies to patients,” said Thiemo Huuk, co-founder and co-CEO of GoSilico, in the press release.

Traditional process development methods are time consuming. “One factor at a time” can take approximately 13 weeks and design of experiments often takes approximately four weeks, but simulation using modelling in digital twins can be a scalable and robust solution within about one week, Cytiva said in the press release. In addition, modeling reduces the amount of experiment materials used.

GoSilico’s products will continue to be known as GoSilico ChromX and GoSilico DSPX for the immediate future and will be integrated into Cytiva immediately, according to the press release.

GoSilico’s software for digital twins of downstream biopharmaceutical processes will be integrated into Cytiva.

Cytiva Acquires German Software Maker GoSilico 

Precision NanoSystems (PNI), a Canadian genetic medicines technology and solutions company, announced on June 1, 2021 that it has been acquired by Danaher Corporation’s Life Sciences platform.

Currently, PNI offers a Genetic Medicine Toolkit, including its GenVoy LNP delivery platform and NanoAssemblr microfluidic-based nanoparticle manufacturing platform, for the development of genetic medicines, the company said in a press release. PNI also plans on developing a new center of manufacturing excellence in Vancouver to enhance its therapeutic and vaccine manufacturing capabilities.

“PNI has advanced a number of exciting innovations, and we’re thrilled to welcome this talented team,” said Emmanuel Ligner, Danaher Group executive, in the press release. “As mRNA has matured as a successful technology in some COVID vaccines, we’re seeing huge potential for this technology to accelerate other therapies. The work done so far by the PNI team will also enable our customers at Cytiva and Pall [also part of Daniher] to take a huge step forward in advancing their science to improve the lives of patients.”

Currently, PNI offers a Genetic Medicine Toolkit, including its GenVoy LNP delivery platform and NanoAssemblr microfluidic-based nanoparticle manufacturing platform, for the development of genetic medicines.

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